The overall goal of the proposed project is to develop a robust and relatively low-cost device that can perform analytical micro-scale titrations on precious NMR samples using pre-existing NMR probes and hardware. Liquid-state, high resolution NMR spectroscopy has proven to be an extremely valuable tool in the biomedical sciences, with applications including the structural and biophysical characterization of biologic macromolecules, physicochemical characterization of small molecules, and the analysis of complex biologic specimens such as human serum, urine and homogenized tissue extracts. A widely utilized experimental protocol involves the collection of successive NMR spectra on a biological specimen during a stepwise titration of a secondary chemical or biological component. Common examples include titration of acid or base in a pH titration to measure site-specific pKa values in macromolecules, titration of a labeled biomolecule (e.g. protein) with a small molecule or another macromolecule for biophysical characterization of ligand-binding, or titrations of chemical mixtures during screening of therapeutic targets for drug development. However, current methodologies for performing these NMR titrations are either prohibitively costly for most academic settings or inefficient in terms of experimental effort or the consumption of often highly precious NMR sample material. In response, we are proposing to develop a low-cost device for automating NMR titrations using a single NMR sample, which could be adapted to any existing, commercial high-resolution NMR spectrometer. Our design fits two motor-driven, non-magnetic syringes to the edges of a standard NMR tube holder (currently used to insert the sample into central bore of the high field magnet), and will include two lengths of small diameter tubing connected to their respective syringes. In a novel application, non-magnetic Piezo-electric motorswill control the syringes, one containing a concentrated solution of titrant and the other dedicated to sample mixing. The availability of such a device would be highly valuable to a wide diversity of biomedical researchers and would have applications in the investigation of essentially all human diseases.